{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T21:52:36Z","timestamp":1784843556819,"version":"3.55.0"},"reference-count":70,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Pisa"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cisplatin is a chemotherapeutic drug for the treatment of several solid tumors, whose use is limited by its nephrotoxicity, neurotoxicity, ototoxicity, and development of resistance. The toxicity is caused by DNA cross-linking, increase in reactive oxygen species and\/or depletion of cell antioxidant defenses. The aim of the work was to study the effect of antioxidant compounds (Lisosan G, Taurisolo\u00ae) or hydrogen sulfide (H2S)-releasing compounds (erucin) in the auditory HEI-OC1 cell line treated with cisplatin. Cell viability was determined using the MTT assay. Caspase and sphingomyelinase activities were measured by fluorometric and colorimetric methods, respectively. Expression of transcription factors, apoptosis hallmarks and genes codifying for antioxidant response proteins were measured by Western blot and\/or RT-qPCR. Lisosan G, Taurisolo\u00ae and erucin did not show protective effects. Sodium hydrosulfide (NaHS), a donor of H2S, increased the viability of cisplatin-treated cells and the transcription of heme oxygenase 1, superoxide dismutase 2, NAD(P)H quinone dehydrogenase type 1 and the catalytic subunit of glutamate-cysteine ligase and decreased reactive oxygen species (ROS), the Bax\/Bcl2 ratio, caspase-3, caspase-8 and acid sphingomyelinase activity. Therefore, NaHS might counteract the cytotoxic effect of cisplatin by increasing the antioxidant response and by reducing ROS levels and caspase and acid sphingomyelinase activity.<\/jats:p>","DOI":"10.3390\/ijms242417416","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T04:14:42Z","timestamp":1702440882000},"page":"17416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of Nutraceuticals on Cisplatin-Induced Cytotoxicity in HEI-OC1 Cells"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8335-4821","authenticated-orcid":false,"given":"Lorenzo","family":"Guidotti","sequence":"first","affiliation":[{"name":"General Physiology Unit, Department of Biology, University of Pisa, Via San Zeno 31, 56127 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Tomassi","sequence":"additional","affiliation":[{"name":"Institute of Agricultural Biology and Biotechnology, Italian National Research Council, Via Moruzzi 1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0730-2648","authenticated-orcid":false,"given":"Silvia","family":"Marracci","sequence":"additional","affiliation":[{"name":"General Physiology Unit, Department of Biology, University of Pisa, Via San Zeno 31, 56127 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7597-123X","authenticated-orcid":false,"given":"Michele","family":"Lai","sequence":"additional","affiliation":[{"name":"Retrovirus Centre, Department of Translational Medicine and New Technologies in Medicine and Surgery, University of Pisa, Strada Statale del Brennero 2, 56127 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominga","family":"Lapi","sequence":"additional","affiliation":[{"name":"General Physiology Unit, Department of Biology, University of Pisa, Via San Zeno 31, 56127 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4785-7282","authenticated-orcid":false,"given":"Rossana","family":"Pesi","sequence":"additional","affiliation":[{"name":"Biochemistry Unit, Department of Biology, University of Pisa, Via San Zeno 31, 56127 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7063-6192","authenticated-orcid":false,"given":"Laura","family":"Pucci","sequence":"additional","affiliation":[{"name":"Institute of Agricultural Biology and Biotechnology, Italian National Research Council, Via Moruzzi 1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2181-2142","authenticated-orcid":false,"given":"Ettore","family":"Novellino","sequence":"additional","affiliation":[{"name":"Facolt\u00e0 di Medicina e Chirurgia, Universit\u00e0 Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Albi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Interno Orto Botanico, University of Perugia, Via Romana, 06126 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1344-2786","authenticated-orcid":false,"given":"Mercedes","family":"Garcia-Gil","sequence":"additional","affiliation":[{"name":"General Physiology Unit, Department of Biology, University of Pisa, Via San Zeno 31, 56127 Pisa, Italy"},{"name":"Interdepartmental Research Center Nutrafood \u201cNutraceuticals and Food for Health\u201d, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ejpb.2021.03.008","article-title":"Cisplatin-induced ototoxicity: Updates on molecular mechanisms and otoprotective strategies","volume":"163","author":"Tang","year":"2021","journal-title":"Eur. 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